Familial Nervous System Tumor Syndromes

Roy E. Strowd, III, MD, MEd, MS; Scott R. Plotkin, MD, PhD Neuro-oncology p. 1523-1552 December 2020, Vol.26, No.6 doi: 10.1212/CON.0000000000000950
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PURPOSE OF REVIEW Although sporadic primary neoplasms account for the majority of nervous system tumors, familial nervous system tumor syndromes are important and clinically relevant conditions for the neurologist to understand. This article reviews common inherited nervous system tumor syndromes including neurofibromatosis type 1, neurofibromatosis type 2, schwannomatosis, tuberous sclerosis complex, and von Hippel-Lindau syndrome. The epidemiology, genetics, approach to diagnosis, neurologic and nonneurologic manifestations, and management options are reviewed.

RECENT FINDINGS Awareness of the more common and clinically relevant familial nervous system tumor syndromes is important. These conditions teach us about the underlying biology that drives tumor development in the central and peripheral nervous systems including peripheral nerve sheath tumors (eg, neurofibroma, schwannoma), meningioma, vestibular schwannoma, subependymal giant cell astrocytoma, and hemangioblastoma. Knowledge of the clinical manifestations ensures that the neurologist will be able to diagnose these conditions, recommend appropriate surveillance, refer to specialists, and support optimal management. Important discoveries in the role of the underlying genetics have contributed to the launch of several novel drug trials for these tumors, which are changing therapeutic options for patients.

SUMMARY Familial nervous system tumor syndromes are uncommon conditions that require specialized surveillance and management strategies. Coordination across a multidisciplinary team that includes neurologists, neuro-oncologists, radiologists, neurosurgeons, radiation oncologists, otolaryngologists, pathologists, neuropsychologists, physical medicine and rehabilitation specialists, and geneticists is necessary for the optimal treatment of these patients.

Address correspondence to Dr Scott Plotkin, Center for Neuro-Oncology and Department of Neurology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, [email protected].

RELATIONSHIP DISCLOSURE: Dr Strowd serves as a consultant for Monteris Medical and Novocure and as a section editor for Neurology. Dr Strowd has received research/grant support from the American Society of Clinical Oncology; Jazz Pharmaceuticals, Inc; the National Institutes of Health (R21CA229027, R21CA248106); and the Southeastern Brain Tumor Foundation. Dr Plotkin has served on research and clinical care advisory boards for the Children’s Tumor Foundation and has received personal compensation as a consultant for AstraZeneca, NFlection Therapeutics, Inc, NF2 Therapeutics, Inc, and SonALAsense and research/grant support from the Children’s Tumor Foundation, the Department of Defense (W81XWH-17-1-0121 and W81XWH-16-1-0103), the National Institutes of Health (5R01CA201130-04, 5K12CA090354-19, 9R13CA236402-03, and 2R42CA192600-02), and the Neurofibromatosis Therapeutic Acceleration Program. Dr Plotkin has held stock in NFlection Therapeutics, Inc, and NF2 Therapeutics, Inc.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Strowd and Plotkin discuss the unlabeled/investigational use of bevacizumab, everolimus, lapatinib, ridaforolimus, selumetinib, and temsirolimus for the treatment of familial nervous system tumors.

© 2020 American Academy of Neurology.